Voltage sensitive dye (VSD) imaging of electrical activity permits the high spatial resolution recording of voltage changes when classical electrodes or patch pipettes are too bulky. M. Canepari and D. Zecevic, editors, 2010, “Membrane Potential Imaging in the Nervous System Methods and Applications”, Springer: New York. Perhaps the ultimate application of optical voltage recording, requiring excellent spatial and temporal resolution, is to probe voltage changes at individual dendritic spines, the fundamental neuronal units for the initial processing of synaptic inputs. This has been recently achieved using second harmonic generation (M. Nuriya, J. Jiang, B. Nemet, K. Eisenthal, and R. Yuste, 2006, “Imaging membrane potential in dendritic spines”, Proc. Natl. Acad. Sci. U.S.A., pages 786-790), confocal linescans (L. M. Palmer and G. J. Stuart, 2009, “Membrane Potential Changes in Dendritic Spines during Action Potentials and Synaptic Input”, The Journal of Neuroscience, volume 29, pages 6897-6903) and a fast CCD camera (K. Holthoff, D. Zecevic, and A. Konnerth, 2010, “Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons”, The Journal of Physiology (London), volume 588, pages 1085-1096) to image spines near the surface of a brain slice. In each case, the VSD was applied intracellularly and allowed to diffuse into the dendritic arbor. In the latter study, a dramatic increase in sensitivity and signal-to-noise permitted visualization of spine voltage changes in single trials. Applying this approach to 2-photon imaging of VSDs (J. A. N. Fisher, J. R. Barchi, C. G. Welle, G. H. Kim, P. Kosterin, A. L. Obaid, A. G. Yodh, D. Contreras, and B. M. Salzberg, 2008, “Two-photon excitation of potentiometric probes enables optical recording of action potentials from mammalian nerve terminals in situ”, Journal of Neurophysiology, volume 99, pages 1545-1553) could improve the measurements still further by permitting deeper penetration of the brain while preserving the sensitivity of fluorescence-based detection.